Deciphering the Mechanisms of Medulloblastoma Treatment Resistance using Integrative Genomics
Medulloblastoma is the most common malignant brain tumor of childhood. Current therapy consisting of surgery, irradiation of the entire brain and spine followed by cytotoxic chemotherapy results in 5 year overall survival rates of approximately 70%. However, two major challenges remain. The first is that recurrent disease is almost uniformly fatal and second, treatment of young children with radiation therapy results in devastating long term side effects. Many studies have been conducted analyzing the genetics of medulloblastoma, but all of these studies have been conducted in the untreated sample from diagnosis, not from recurrences.
As such, I have collected 50 pairs of medulloblastoma from both diagnosis and recurrence. This includes recurrences in the original tumor bed and distant recurrences along the surface of the brain and/or spinal cord. In this application, I am proposing to profile these paired samples using advanced genomic techniques. This will allow us to compare the genetics of the primary sample to the recurrence, thus shedding light on mechanisms of treatment resistance. This will allow us to identify pathways and mechanisms driving treatment resistance which can then be validated. This project has the potential of uncovering new and novel pathways which can be translated into clinical trials for children with recurrent medulloblastoma.